Heparanase-neutralizing A54 monoclonal antibody

Abstract

The present invention relates to an heparanase-binding and heparanase-neutralizing monoclonal antibody (IgG-1 mAb A54), including its epitope (HBD-II) and mode of interaction with heparanase, pharmaceutical composition comprising same, and uses thereof e.g. for inhibiting or treating a disease or disorder associated with heparanase activity, including but not limited to cancer, inflammation, viral infection, diabetes and related complications. The present invention further provides combinatorial cancer therapies, comprising the heparanase-neutralizing mAb and an additional anti-cancer treatment such as chemotherapy or radiation.

The invention claimed is: 
     
         1 . An antibody or an antigen-binding fragment, analog or derivative thereof, directed against a heparanase enzyme, wherein the antibody, antigen-binding fragment, analog or derivative thereof comprises six complementarity-determining regions (CDRs), of SEQ ID NO: 1 to SEQ ID NO: 6. 
     
     
         2 . The antibody or antigen-binding fragment, analog or derivative of  claim 1 , wherein said antibody or antigen-binding fragment, analog or derivative is murine or human or is humanized. 
     
     
         3 . The antibody or antigen-binding fragment, analog or derivative of  claim 1 , comprising the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 8. 
     
     
         4 . The antibody or antigen-binding fragment, analog or derivative of  claim 1 , wherein the antibody fragment is selected from the group consisting of: Fab, Fab′, F(ab′)2, Fd, Fd′, Fv, dAb, isolated CDR region, single chain antibody, diabodies, and linear antibodies. 
     
     
         5 . A pharmaceutical composition comprising the antibody or antigen-binding fragment, analog or derivative of  claim 1  and a pharmaceutical acceptable carrier. 
     
     
         6 . An isolated polynucleotide sequence encoding the antibody of  claim 1 . 
     
     
         7 . The isolated polynucleotide sequence of  claim 6 , comprising the nucleotide sequence as set forth in SEQ ID NO: 9 to SEQ ID NO: 16. 
     
     
         8 . A vector comprising the polynucleotide sequence of  claim 6 . 
     
     
         9 . A cell comprising the antibody or antigen-binding fragment, analog or derivative of  claim 1 . 
     
     
         10 . A cell comprising the isolated polynucleotide sequence of  claim 6 . 
     
     
         11 . A cell comprising the vector of  claim 8 . 
     
     
         12 . A pharmaceutical composition comprising the isolated polynucleotide sequence of  claim 6  and a pharmaceutically acceptable carrier. 
     
     
         13 . A pharmaceutical composition comprising the vector of  claim 8  and a pharmaceutically acceptable carrier.